This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Individuals respond very differently to infection with HIV leading to highly variable courses of disease post infection. This proposal aims to investigate a mechanism of natural immunosurveillance, termed "natural killer cells" (NK) that besides monitoring cells in the body for senescence (being too old to function properly) also sense deviation from the "normal" at the cell level. We have found that similar to the major histocompatibility complex (MHC) genes that constitute an organism's ID and dictate many of the antigen specific immune responses, innate responses also may vary due to genetic inheritance. The application will therefore focus on rhesus macaques with comparable MHC genes but distinct NK associated receptors to correlate distinct receptors with susceptibility to simian immunodeficiency (SIV) induced disease. The proposal will also address the impact of NK inhibition during acute infection on the disease course and finally whether this mechanism can be boosted by providing additional NK in vivo and whether such boost has impact on virus replication, the quality of the ensuing adaptive immune responses and disease course. All studies will investigate blood, rectal, colon and small bowel biopsies as well as broncholveolar lavages (BAL) to monitor the effect of NK before and after infection with SIVmac251.